safety, tolerability, pharmacokinetics, and preliminary efficacy of btx-9341 in advanced and/or metastatic breast cancer

Conditions: Breast Cancer

Summary: the purpose of this study is to test btx-9341 alone or in combination with fulvestrant (a currently marketed medication for breast cancer) in participants with advanced and/or metastatic hormone receptor positive (hr+)/human epidermal growth factor receptor 2 negative (her2-) breast cancer. the study includes a dose escalation part (part a) where small groups of participants will receive increasing doses of btx-9341 or btx-9341 + fulvestrant followed by a dose expansion part (part b) where participants will receive the dose of btx-9341 selected in part a + fulvestrant.

this first-in-human (fih), phase 1 study of btx-9341 is multicenter, nonrandomized, and open-label to evaluate the safety, tolerability, pharmacokinetics (pk), and preliminary efficacy of btx-9341 in participants with advanced and/or metastatic hr+/her2 breast cancer. the study will include a dose escalation part (part a) followed by a dose expansion part (part b). during part a, btx-9341 will initially be dose escalated alone and then in combination with fulvestrant. a single combination therapy cohort of btx-9341 + fulvestrant will be further explored in part b. btx-9341 will be administered orally in 28-day treatment cycles.

Eligibility criteria:
inclusion criteria: * metastatic and/or locally advanced hr+/her2- breast cancer (dose escalation: measurable disease and/or at least 1 lytic or mixed \[lytic + sclerotic\] bone lesion that can be assessed by ct or mri or non-measurable disease \[including bone lesions\]; dose expansion: measurable disease) * dose escalation: (a) received not more than 1 chemotherapy in the metastatic/advanced setting; (b) no limit to the lines of endocrine therapy (monotherapy or combination therapy) in the metastatic setting; (c) received cdk4/6 inhibitor therapy * dose expansion: (a) received not more than 1 chemotherapy in metastatic/advanced setting; (b) received not more than 2 lines of endocrine therapy (monotherapy or combination therapy) and must have been on prior endocrine therapy for at least 6 months before progression; (c) received at most 2 lines of cdk4/6 inhibitor therapy (1 in the adjuvant setting and 1 in the metastatic setting) and must have been on prior cdk4/6 inhibitor therapy for at least 6 months * acceptable hematologic function 1. anc ≥ 1500 per ml. note: use of growth-factors to maintain the anc criterion is prohibited. 2. platelet count ≥ 100,000 per ml. note: use of transfusions or thrombopoietic agents to achieve the baseline platelet count criterion is prohibited. 3. hemoglobin ≥ 9.0 g/dl. note: packed red blood cell transfusion is allowed up to 14 days prior to trial entry. * acceptable liver function 1. bilirubin ≤ 2.0 × institutional upper limit of normal (uln) (or \< 3.0 × institutional uln if gilbert's disease is present) 2. alanine transaminase (alt)/aspartate aminotransferase (ast) ≤ 3.0 × institutional uln (≤ 5.0 × institutional uln if liver metastases present) 3. alkaline phosphatase ≤ 2.5 × institutional uln (≤ 5.0 × institutional uln if bone or liver metastases present) * able and willing to sign informed consent * meets all study requirements in the opinion of the investigator exclusion criteria: * rb1 (retinoblastoma) gene mutation * symptomatic visceral disease * clinical evidence or history of central nervous system metastasis * abnormalities in coagulation, such as bleeding diathesis, or treatment with anticoagulants precluding injections of fulvestrant or luteinizing hormone-releasing hormone (lhrh) agonist

Keywords: hr+/her2-